title: Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect.
abstract: Metabolic reprogramming in cancer is manifested by persistent aerobic glycolysis and suppression of mitochondrial function and is known as the Warburg effect. The Warburg effect contributes to cancer progression and is considered to be a promising therapeutic target. Understanding the mechanisms used by cancer cells to suppress their mitochondria may lead to development of new approaches to reverse metabolic reprogramming. We have evaluated mitochondrial function and morphology in poorly respiring LM7 and 143B osteosarcoma (OS) cell lines showing the Warburg effect in comparison with actively respiring Saos2 and HOS OS cells and noncancerous osteoblastic hFOB cells. In LM7 and 143B cells, we detected markers of the mitochondrial permeability transition (MPT), such as mitochondrial swelling, depolarization, and membrane permeabilization. In addition, we detected mitochondrial swelling in human OS xenografts in mice and archival human OS specimens using electron microscopy. The MPT inhibitor sanglifehrin A reversed MPT markers and increased respiration in LM7 and 143B cells. Our data suggest that the MPT may play a role in suppression of mitochondrial function, contributing to the Warburg effect in cancer.
authors.affiliation: From the Center for Musculoskeletal Research and.
authors.forename: An-Hoa
authors.initials: AH
authors.lastname: Giang
authors.forename: Tamara
authors.initials: T
authors.lastname: Raymond
authors.forename: Paul
authors.initials: P
authors.lastname: Brookes
authors.forename: Karen
authors.initials: K
authors.lastname: de Mesy Bentley
authors.forename: Edward
authors.initials: E
authors.lastname: Schwarz
authors.forename: Regis
authors.initials: R
authors.lastname: O'Keefe
authors.forename: Roman
authors.initials: R
authors.lastname: Eliseev
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006019:Glycolysis; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D012516:Osteosarcoma / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption; D010539:Permeability
keywords: Cancer; Cyclophilin D; Glycolysis; Mitochondria; Mitochondrial Permeability Transition; Osteosarcoma; Warburg Effect